Study on role of GANT-61 as Gli inhibitor on epithelial-mesenchymal transition of lung cancer / 重庆医学

ABSTRACT

Objective To research the effect of GANT61 on epithelial‐mesenchymal transition (EMT) in human lung cancer H1703 and A549 cells lines ,and to preliminarily investigate its action mechanism .Methods DMSO was used as the control(DMSO group) .After treating H1703 and A549 cells with GANT61 for 24 h ,the gene changes of Gli‐1 ,Gli‐2 ,E‐cadherin and Vimentin were detected by using the real time fluorescence quantitative PCR method .The influence of GANT61 on the expression of E‐cad‐herin and Vimentin protein after acting on H1703 and A549 cells was observed by using the Western blotting assay .The scratch healing test was performed to evaluate the effect of GANT 61 on the tumor cell invasion ability after acting on H1703 and A549 cells .Results The real time fluorescence quantitative PCR showed that ,compared with the DMSO group ,GANT61 down‐regulated the mRNA expression of Gli‐1 ,Gli‐2 and Vimentin mRNA of H1703 and A549 cell lines and elevated the expression of E‐cadherin protein(P<0 .01);the Western blotting showed that GANT61 down‐regulated the expression of Vimentin of H1703 and A549 cell lines ,and elevated the expression of E‐cadherin(P<0 .01);the scratch healing test revealed the invasion ability of H 1703 and A549 cells in the GANT61 treatment group was significantly decreased (P<0 .01) .Conclusion EMT in lung cancer is related with aber‐rant activations of Gli1 and Gli2 in Hedgehog signal transduction pathway ,GANT61 could influence the EMT ability in lung cancer cells by down‐regulating the expression of Gli‐1 and Gli‐2 .Gli could become a new molecular target for inhibiting the lung cancer cell metastasis.